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Cellular and Molecular Neurobiology

, Volume 37, Issue 4, pp 717–728 | Cite as

Parkin Overexpression Ameliorates PrP106–126-Induced Neurotoxicity via Enhanced Autophagy in N2a Cells

  • Sher Hayat Khan
  • Deming Zhao
  • Syed Zahid Ali Shah
  • Mohammad Farooque Hassan
  • Ting Zhu
  • Zhiqi Song
  • Xiangmei Zhou
  • Lifeng Yang
Original Research

Abstract

Transmissible spongiform encephalopathies (TSEs) are caused by the accumulation of the abnormal prion protein scrapie (PrPSc). Prion protein aggregation, misfolding, and cytotoxicity in the brain are the major causes of neuronal dysfunction and ultimate neurodegeneration in all TSEs. Parkin, an E3 ubiquitin ligase, has been studied extensively in all major protein misfolding aggregating diseases, especially Parkinson’s disease and Alzheimer’s disease, but the role of parkin in TSEs remains unknown. Here we investigated the role of parkin in a prion disease cell model in which neuroblastoma2a (N2a) cells were treated with prion peptide PrP106–126. We observed a gradual decrease in the soluble parkin level upon treatment with PrP106–126 in a time-dependent manner. Furthermore, endogenous parkin colocalized with FITC-tagged prion fragment106–126. Overexpression of parkin in N2a cells via transfection repressed apoptosis by enhancing autophagy. Parkin-overexpressing cells also showed reductions in apoptotic BAX translocation to the mitochondria and cytochrome c release to the cytosol, which ultimately inhibited activation of proapoptotic caspases. Taken together, our findings reveal a parkin-mediated cytoprotective mechanism against PrP106–126 toxicity, which is a novel potential therapeutic target for treating prion diseases.

Keywords

PrP106–126 Parkin Apoptosis Prion diseases Cytotoxicity Autophagy 

Notes

Acknowledgments

This work was supported by the Natural Science Foundation of China (No. 31272532) and the Foundation of Chinese Ministry of Science and Technology (Project No. 2015BAI07B02).

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sher Hayat Khan
    • 1
  • Deming Zhao
    • 1
  • Syed Zahid Ali Shah
    • 1
  • Mohammad Farooque Hassan
    • 1
  • Ting Zhu
    • 2
  • Zhiqi Song
    • 1
  • Xiangmei Zhou
    • 1
  • Lifeng Yang
    • 1
  1. 1.National Animal Transmissible Spongiform Encephalopathy Laboratory, Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of AgrobiotechnologyChina Agricultural UniversityBeijingChina
  2. 2.Fujian Agriculture and Forestry UniversityFuzhouChina

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